A 28-year-old woman with newly diagnosed tuberculosis is counselled about the teratogenic potential of antitubercular drugs. Which of the following first-line antitubercular agents is the most common cause of teratogenicity and is therefore contraindicated in pregnancy?

Explanation

## Teratogenicity of First-Line Antitubercular Drugs in Pregnancy **Key Point:** Pyrazinamide (PZA) is the most common first-line antitubercular agent contraindicated in pregnancy due to documented teratogenic effects and is therefore omitted from the regimen in pregnant women. ### Safety Profile of First-Line TB Drugs in Pregnancy | Drug | Pregnancy Category | Teratogenicity Risk | Use in Pregnancy | |------|---|---|---| | **Isoniazid** | A | Minimal; well-established safety | **Safe** — use | | **Rifampicin** | C | Low; no confirmed teratogenicity | **Safe** — use | | **Pyrazinamide** | C | **Documented teratogenicity** | **Contraindicated** — avoid | | **Ethambutol** | B | Low; optic neuritis risk, not teratogenicity | **Safe** — use with caution | **High-Yield:** The standard regimen in pregnant women is **INH + RIF + ETH** (without PZA) for the intensive phase, followed by INH + RIF for the continuation phase, extending total duration to 9 months. ### Pyrazinamide — Teratogenic Mechanism 1. **Animal studies:** Documented fetal abnormalities and skeletal defects 2. **Human data:** Limited but concerning reports of congenital anomalies 3. **WHO stance:** Contraindicated in pregnancy due to insufficient safety data and documented animal teratogenicity 4. **Clinical consequence:** Omitted from first-line regimen in pregnant TB patients **Clinical Pearl:** A woman of childbearing age diagnosed with TB should be counselled about contraception during treatment (especially with RIF, which induces oral contraceptive metabolism) and the need for extended therapy if pregnant. **Warning:** ~~Ethambutol is contraindicated in pregnancy~~ — Ethambutol is actually safe; the concern is optic neuritis (visual toxicity), not teratogenicity. It is included in the pregnant TB regimen. ### Regimen Modification in Pregnancy ```mermaid flowchart TD A[TB diagnosis in pregnant woman]:::outcome --> B[Standard first-line regimen?]:::decision B -->|Standard HRZE| C[Omit PZA]:::action B -->|Modified HRE| D[INH + RIF + ETH for 2 months]:::action D --> E[INH + RIF for 7 months]:::action C --> E E --> F[Total 9 months therapy]:::outcome ``` **Mnemonic: "PZA out, ETH in"** — Pyrazinamide is excluded; Ethambutol is included in pregnant TB patients.